Liver repopulation by c-Met-positive stem/progenitor cells isolated from the developing rat liver

Area of Science:

• Hepatology
• Stem Cell Biology
• Developmental Biology

Background:

• Self-renewing stem cells are crucial for tissue development and regeneration.
• Hepatic stem cells express the hepatocyte growth factor receptor c-Met in developing mouse liver.
• Investigating c-Met as a universal marker for hepatic stem cells across species is essential for isolation.

Purpose of the Study:

• To determine if c-Met is an essential marker for hepatic stem cells in rats.
• To assess the in vivo liver-repopulation potential of sorted fetal rat-derived c-Met+ cells.
• To validate c-Met as a potential marker for hepatic stem cells in various animal strains, including humans.

Main Methods:

• Fetal rat liver cells were fractionated using flow cytometry with antibodies for c-Met and CD45.
• Sorted cell subpopulations (c-Met+ CD45- and c-Met- CD45+) were transplanted into retrorsine-treated adult rats undergoing hepatectomy.
• Liver repopulation was analyzed qualitatively and quantitatively at 9 months post-transplant.

Main Results:

• Transplantation of c-Met+ CD45- sorted cells led to the formation of colonies containing mature hepatocytes expressing albumin and glycogen.
• c-Met- cells and CD45+ cells failed to repopulate the damaged recipient livers.
• High enrichment of liver-repopulating cells was achieved by sorting c-Met+ cells.

Conclusions:

• c-Met+ cell sorting effectively enriches for liver-repopulating cells in developing rat liver.
• The c-Met/HGF interaction is critical for stem cell growth, differentiation, and self-renewal during rat liver organogenesis.
• c-Met is a promising essential marker for hepatic stem cells in various animal strains, potentially including humans.